Difluoroxalatostannate(ii)complexes

ABSTRACT

A NEW GENUS IF COMPOSITIONS IF MATTER, NAMELY, DIFLUOROXALATOSTANNATE (II) COMPLEXES HAS BEEN DISCOVERED. THESE COMPOUNDS WHEN INCORPORATES INTO ORAL COMPOSITIONS FOR DENTAL CARIES PROPHYLAXIS (E.G., AS A CONSTITUENT OF A DENTIFRICE, PROPHYLAXIS PASTE, OR MOUTHWASH), HAVE DEMONSTRATED SUBSTANTIAL UTILITY AS AN ANTICARIOGENIC AGENT.

United States Patent 3,721,691 DIFLUOROXALATOSTANNATEGI) COMPLEXES Simon Katz, Indianapolis, Ind., assignor to Indiana University Foundation, Bloomington, Ind.

No Drawing. Original application Jan. 20, 1971, Ser. No. 108,227. Divided and this application Mar. 2, 1971, Ser. No. 231,434

Int. Cl. C07f 7/22 US. Cl. 260429.7 4 Claims ABSTRACT OF THE DISCLOSURE A new genus of compositions of matter, namely, difluoroxalatostannatefll) complexes has been discovered. These compounds when incorporated into oral compositions for dental caries prophylaxis (e.g., as a constituent of a dentifrice, prophylaxis paste, or mouthwash), have demonstrated substantial utility as an anticariogenic agent.

BACKGROUND OF THE INVENTION This is a division of application Ser. No. 108,227, filed Jan. 20, 1971, now US. Pat. No. 3,678,153.

Field of the invention This invention relates to a new genus of compounds, difluoroxalatostannate(II) complexes and to the use thereof as anticariogenic agents in oral compositions for caries prophylaxis. By the term oral composition is meant a product which in the ordinary course of usage is not intentionally ingested, but rather is retained in the oral cavity so as to contact the oral hard tissues.

Description of the prior art It is commonly recognized that the presence of microquantities of fluoride in drinking water (e.g., 1.0 microgram fluoride per milliliter) has a pronounced effect on reducing the incidence of dental caries in permanent teeth of children consuming such water from birth through eight years of age. Fluoride salts have been introduced into public water supplies in many communities with good results. This method of caries prophylaxis is not available, however, to a large number of people whose drinking water is obtained from small, private fluoride-deficient sources such as individual wells, etc. Further, the addition of fluoride to common public water sources is not always accepted or permitted.

Topical applications of aqueous fluoride solutions by example, sodium fluoride (NaF) is only soluble to the extent of about 4% in water. Solubility can, of course, limit the quantity of anticariogenic ions provided by an agent that is available for reaction with the tooth surface. The relative insolubility of certain of the prior art anticariogenic agents limits the value of the same for the use in prophylactic paste compositions since the volume of water in prophylactic paste is substantially limited.

Finally, certain of the known prior art anticariogenic agents have been relatively unstable in aqueous solutions. For example, stannous ions are subject to oxidation and hydrolysis and, for that reason stannous containing compositions must ordinarily be in freshly prepared form or must be used in conjunction with complexing anions in order to obtain its optimal anticariogenic eflect.

For these reasons and others, dental researchers have continued their efforts to develop new compositions which are not only anticariogenically more effective, but which also exhibit none of the difficulties associated with certain of the prior art anticariogenic agents.

It is generally believed that fluoride ion in functioning as a topical anticariogenic agent acts through the formation of insoluble calcium fluoride on the surface of the tooth enamel. It has also been suggested that the incorporation of fluoride into the enamel lattice through the substitution of fluoride for hydroxyl groups in the hydroxyapatite crystal of the enamel (so as to form fluoridesubstituted hydroxyapatite) decreases the solubility of the enamel in oral acids.

The degree of the reaction between the fluoride and the enamel is limited by the relatively close proximity of the enamel crystals and by the formation of the calcium fluoride precipitate itself. In fact, the proximity between enamel crystals (Which serves to prevent the passage of fluoride ions into the crystal lattice) has been suggested to be the main factor limiting the deep penetration of topical fluoride into the enamel crystal lattice. In addition to the electrostatic and mechanical barriers posed by the close proximity of the enamel crystal, a second factor apparently limiting the possibility of fluoride uptake is the energy required for the fluoride-enamel reaction to proceed.

Because of the limitations posed on fluoride uptake, it would be desirable to provide a means for increasing the fluoride uptake and penetration into the enamel lattice, and this invention therefore has for its principal object to provide a new genus of compounds, difluoroxaltatostannatefll) complexes, which increase the uptake of the fluoride ion by and reduce the acid solubility of dental enamel.

It is a further related object of the present invention to provide a new genus of compounds, difluoroxalatostannate(II) complexes, which exhibit a high level of anticariogenic effectiveness and which are nontoxic to living organisms at operable concentration levels.

A further object is to provide an adjunct to a topical fluoride system capable of temporarily loosening the enamel crystal lattice so as to permit fluoride ions to penetrate deeper, serving also to reduce the lattice energy so as to decrease the amount of energy required for a fluoride-enamel reaction to proceed.

Yet another object of the present invention is to provide an anticariogenic agent of the character described which is stable in aqueous solutions even at relatively high concentration.

Another object is to provide new and unique oral compositions characterized by the inclusion of a chelating agent in combination with a source of soluble fluoride ion or of a chelating agent complexed to a fluoride moiety.

A related object involves the provision of oral compositions comprising a source of soluble fluoride ion and a chelating agent to enhance the uptake of fluoride ion by the reduction of enamel solubility of dental enamel.

Yet another object is to provide new and improved methods for topically reducing the incidence of dental caries.

Another object is to provide a new method of increasing the uptake of tin(II) ions into the dental enamel crystal lattice.

SUMMARY OF THE INVENTION The foregoing and other objects, advantages, and features of this invention may be achieved with new and more effective oral compositions for caries prophylaxis which utilize new compositions of matter, difluoroxalatostannate(II) complexes, as anticariogenic agents. Such oral compositions (which may take the form of dentifrices, prophylactic pastes, topical solutions, and mouthwashes) comprise from about 0.1 to by Weight of the difluoroxalatostannate(II) complexes.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In accordance with the present invention, there have been discovered new compositions of water, namely di fluoroxalatostannate(II) complexes of the formula where M+ is a metal or ion such as potassium, sodium or ammonium. In addition, water of hydration may be present in the molecule. The difluoroxalatostannate(II) complexes of this invention have, as will hereinafter be described in detail, demonstrated effectiveness as anticariogenic agents useful in oral compositions.

PREPARATION AND PROPERTIES Difluoroxalatostannate(II) complexes may be prepared by various methods. In order to utilize the chelating ability of oxalic acid, H C O plus the known cariostatic effect of tin(II) ions, the use of stannous oxalate was thought to be advantageous. Stannous oxalate, SnC O is, however, insoluble in water. However, upon addition of sodium fluoride, NaF, it was discovered that the stannous oxalate precipitate became soluble. Complete solubility and complete transparency of the solution was found to occur when the fluoride salt was added to the oxalate salt in a 2:1 molar ratio. The pH of the resulting solution is 4.8. It was found that stannous oxalate reacts similarly with potassium fluoride KF-ZH O, to provide a soluble product where the fluoride to oxalate ratio was 2:1.

Another method of preparing the difluoroxalatostannate(II) complexes of this invention involves the utilization of alkali metal hydroxides and hydrofluoric acid. A one mole stannous oxalate suspension having a pH of about 3.0 is prepared. Upon the addition of two moles of hydrofluoric acid, HF, the pH is reduced to 1.7-1.8 but the suspension remains turbid under stirring. Upon the addition of diluted sodium hydroxide, NaOH, the solution becomes clear when the pH approaches 4. 8.

Another method of preparing the difluoroxalatostannate(II) complexes of this invention involves the use of the alkali metal oxalate and stannous fluoride. One mole of the metal oxalate (sodium or potassium oxalate) is 4 slowly added to a solution containing one mole of stannous fluoride. The pH of the solution at that point will be found to be 4.8.

The products of the reactions described above, were separated from their respective solutions through evaporation to almost dryness followed by precipitation by alcohol and dessication under a vacuum over silica gel. The resulting products were White crystalline solids. They are extremely soluble in water, but insoluble in alcohol. Solutions of these compounds are clear at pHs up to approximately 5.5. Above pH 5.5 a whitening of the solution occurs, and a white precipitate can be observed. Some whitening also occurs at pH 5.0 as a function of solution aging.

Further, it was noted that the sodium complex, sodium difluoroxalatostannate(II), Na [SnF (C O has a melting point between 280' and 285 C., and the potassium complex, potassium difluoroxalatostannate(II),

has a melting point between 230 and 240 C.

Sodium difluoroxalatostannate(II) may be conveniently prepared by mixing 10.0 g. of stannous oxalate into ml. of redistilled water. 406 g. of sodium fluoride are mixed into the solution. The product of this reaction may be separated by evaporation as discussed above. Similarly, potassium di-fluoroxalatostannate(II) may be conveniently prepared by mixing 10 g. of stannous oxalate into 100 ml. of redistilled water and mixing into that solution 5.6 g. of potassium fluoride. 9.2 g. of potassium fluoride dihydrate (KF-ZH O) can be substituted for the 5.6 g. of potassium fluoride in this latter reaction. The products of these reactions may be separated by evaporation as discussed above. Following a similar procedure, the ammonium difluoroxalatostannate(II) may be conveniently prepared by dissolving 4.13 g. stannous fluoride in 200 ml. distilled water. While stirring this mixture, 3.72 g. ammonium oxalate monohydrate is added. The products of this reaction may be separated by evaporation as discussed above.

It was further observed, by X-ray diffraction, that the product of the reaction of sodium oxalate and stannous fluoride was identical to that formed by stannous oxalate and sodium fluoride. Similarly, the product of potassium oxalate and stannous fluoride was identical to that obtained with stannous oxalate and potassium fluoride. Both potassium difluoroxalatostannate(II) and sodium difluoroxalatostannate(II) have been characterized according to the conventional Hull-Debye-Scherrer -Xray diflraction powder technique in order to produce a film record. Exposures were made using standard X-ray diffraction camera (diameter 114.7 mm.). As is well known to one skilled in the art, the technique causes crystalline materials to ditfract X-rays according to a pattern specific for each compound. The X-rays expose a film according to a specific pattern, which appears on the film as characteristic lines, the interplanar spacing and the relative intensity of which may be measured in order to identify the compound. The pattern for potassium stannous fluoroxalate and sodium stannous fluoroxalate are distinctive and distinguish these compounds from other compounds, parctlicularly the starting materials from which they are ma e.

ORAL COMPOSITIONS COMPRISING DIFLUOROXALATOSTANNATEUI) COMPLEXES The difluoroxalatostannate (II) complexes of this invention have demonstrated utility as anticariogenic agents for use in oral compositions which comprise carriers such as abrasives, Water, and other nontoxic materials, in addition to the difiuoroxalatostannate(H) complexes of this invention. The compounds of this invention may be applied to the teeth in simple aqueous solution form (as a topical treatment or in the form of an aqueous mouthwash). However, they are also Well suited for use in other oral compositions for caries prophylaxis (e.g., dentifrices and prophylaxis pastes) which contain one or more ionically compatible adjuvants. In general, oral compositions produced in accordance with the present invention comprise from about 0.1 to about by weight of one or more difiuoroxalatostannates.

Oral compositions designed for relatively frequent use, such as dentifrices and mouthwashes, will contain lower levels of difluoroxalatostannatefll) complexes than compositions which are applied less frequently (e.g., prophylactic pastes and topical solutions). Thus dentifrices preferably contain from about .1% up to about 1.5% by weight of difluoroxalatostannate(II) complexes, whereas propylaxis pastes preferably comprise about 2 to 10% metal difluoroxalatostannate (II) complexes by weight and aqueous topical solutions preferably comprise about 1.0 to 8.0% difluoroxalatostannate(II) complexes.

The cleaning and polishing material in dentrifices of this invention should be ionically compatible with tin(II) and fluoride ions and can comprise from about to 95% by weight of the total composition. Preferably, toothpastes contain from 20 to 60% cleaning and polishing agent by weight, and tooth powders contain from 60 to 95 by weight. Examples of suitable cleaning and polishing agents suitable for use in a dentifrice include, without limitation, calcium pyrophosphate, ca P O calcium hydrogen phosphate dihydrate, CaHPO -2H O; insoluble sodium metaphosphate, (NaPO calcium carbonate, CaCO melamine formaldehyde resins (US. Pat. No. 3,070,510); and preferably zirconium silicate and mixtures of zirconium silicate with other cleaning and polishing agents as disclosed in US. Pat. No. 3,450,813. Mixtures of these cleaning and polishing agents may also be used.

Toothpastes require a binder substance to impart desired texture properties. Natural gum binders such as gum tragacanth, gum karaya, gum arabic, etc., and seaweed derivatives such as Irish moss, and alginates, and water soluble cellulose derivatives such as hydroxyethyl cellulose and sodium carboxymethyl cellulose, can be used for this purpose. Desirably, those materials are employed which are most compatible with the fluoride ion. Binders which have no ionic groups, such as hydroxyethyl cellulose, are especially preferred. Improvements in texture can also be attained by including an additional material such as colloidal magnesium aluminum silicate.

Thickening agents in an amount of from 0.5% to 5.0% by weight can be used to form a satisfactory toothpaste.

Toothpaste conventionally contains sudsing agents. Suitable sudsing agents include, but are not limited to, watersoluble alkyl sulfates having from 8 to 18 carbon atoms in the alkyl radical, such as sodium lauryl sulfate, watersoluble salts of sulfonated monoglycerides, fatty acids having fiom 10 to 18 carbon atoms in the alkyl radical such as sodium coconut monoglyceride sulfonate, salts of the fatty acid amides of taurines such as sodium-N-methyl palmitoyl tauride, and salts of fatty esters of isethionic acid.

Sudsing agents can be used in the compositions of this invention in the amount from about 0.5% to about 5.0% by weight of the total composition.

It is also desirable to include some humectant material in toothpaste to keep it from hardening. Materials commonly used for this purpose include glycerine, sorbitol and other polyhydric alcohols. Humectants can comprise up to 35% of the toothpaste composition.

Flavoring materials may be included in the toothpaste formulation, including small amounts of oils of wintergreen and peppermint, and sweetening agents such as saccharine, dextrose and levulose.

Exemplary dentifrice formulations are given in the following examples.

6 EXAMPLE I Constituent: Percent by weight Potassium difluoroxalatostarmatefll) 0.87 Distilled water 18.00 Sorbitol 29.00 BuflYer (KH phthalate) 1.20 Fumaric acid 0.15 Victamide 3.46

Ammonium hydroxide (to adjust pH) approx 0.61 Veegum 0.40 Sodium alkyl sulfate 2.10 Calcium pyrophosphate 32.00 Zirconium silicate 10.50 Binder (Keltrol) 1.00 Saccharin 0.08 Flavor 0.61

*An ammonium salt of a condensation product of N113 and P4010 commercially available from the Victor Chemical Company under the trademark, Vietamide, e.g.,

Constituent: Percent by weight Potassium difluoroxalatostaunate (II) 0.87 Distilled water 20.00 Sorbitol 13.00 Buffer (KI-l phthalate) 1.20 Fumaric acid 0.20

Ammonium hydroxide '(to adjust pH) approx 0.33 Veegum 0.40 Sodium laryl sulfate 1.80 Acid washed talc 30.00 Zirconium silicate 12.00 Glycerin 15.00 Binder (CMC) 4.50 Flavoring agents 0.68

EXAMPLE I11 Constituent: Percent by weight Sodium difluoroxalatostaunate (II) 0.74 Distilled water 18.00 Sorbitol 13.60 Buffer (KH phthalate) 1.20 Hydroxyethylenediaminotetraacetic acid 0.10

Ammonium hydroxide (to adjust pH) approx 0.75 Veegum 0.40 Sodium alkyl aryl sulfonate 2.00 Resin abrasive* 42.00 Glycerin 15.50 Carboxymethylcellulose 5.00 Flavoring agents 0.70

*UJS. Pat. No. 3,070,510

7 EXAMPLE IV Constituent: Percent by weight Ammonium difluoroxalatostannatefll) 0.72 Distilled water 18.00 Glycerin 15.00 Sorbitol 15.00 Buqer (KH phthalate) 1.20 Fumaric acid 0.20

Potassium hydroxide (to adjust pH) approx 0.78 Veegum 0.40 Sodium alkyl sulfate 2.00 Dicalcium phosphate dihydrate 33.55 Dicalcium phosphate, anhydrous 7.45 CMC (binder) 5.00 Flavoring agents 0.70

EXAMPLE V Constituent: Percent by weight Sodium difiuoroxalatostannate(II) 0.75 Distilled water 22.00 Sorbitol 12.00 Methyliminodiacetic acid 0.10 Buffer (KH phthalate) 1.20 Irnidazole (to adjust pH) approx 0.85 Sodium lauryl sulfate 2.00 Calcium pyrophosphate 42.00 Veegum 0.40 Glycerin 14.00 CMC 4.00 Flavoring agents 0.70

An exemplary formulation of a nonabrasive dentifrice is given in the following examples.

EXAMPLE VI-(NON-ABRASIVE DENTIERICE) Constituent: Percent by weight Potassium difluoroxalatostannate(II) 0.87 Distilled water 40.00 Sorbitol 30.00 Fumaric acid 00.15 Buffer (KH phthalate) 1.00 Imidazole (to adjust pH) approx 0.26 Sodium alkyl sulfonate 2.00 Glycerin 19.00 Keltrol 6.00 Flavoring agents 0.70

EXAMPLE VII-( NON-ABRASIVE DENTIFRIOE) Prophylactic paste compositions containing metal di-' fluoroxalatostannate(-II) complex compounds constitute another preferred embodiment of this invention. Such prophylactic paste compositions contain the usual components, including a compatible abrasive such as lava pumice or especially zirconium silicate at a level of about 30% to 80% by weight to form a prophylactic paste composition for use by dentists or dental hygienists in periodic cleaning and polishing of the teeth.

8 Exemplary prophylactic pastes are given in the following examples.

EXAMPLE VIII-(PROPHYLACTIC PASTE) EXAMPLE IX-(PROPHYLACTIC PASTE) Constituent: Percent by weight Sodium difluoroxalatostannate(II) 10.60 Zirconium silicate 49.00 Stannous oxide 5.00

Water 20.00 Glycerin 2.50 Sorbitol 2.00

Veegum 0.70 CMC 1.20 Sodium trimetaphosphate 8.00 Flavoring agents 1.00

ANTICARIOGENIC EFFECTIVENESS The anticariogenic effectiveness of alkali metal stannous fiuoroxalate complexes may be demonstrated by the in vitro tests with whole human teeth or the in vivo dental caries experience in rats (standard experimental animals for anticariogenic studies). The effect of various compositions in reducing the rate of dissolution of dental enamel in acid is also a reliable indicator of anticariogenicity. The eiTect of different dental compositions on the rate of acid dissolution of enamel may be determined by a number of tests well known in the art. The particular test described herein comprises a comparison of acid dissolution of a given tooth after an in vitro treatment with a given test composition. The comparison is expressed as ESR, that is, enamel solubility reduction and the procedure employed is well accepted and has been described in detail previously (Buttner and Muhler, J. D. Res, 36: 897, 1957).

The results of test utilizing solutions comprising potassium difluoroxalatostannate(II) having a fluoride ion content of at least 1,000 p.p.m. and a pH of 5.0 are presented in Table 1. These data illustrate an ESR of approximately 95.4% or more. These data illustrate that the difiuoroxalatostannate(II) complexes demonstrate substantial anticariogenic efficacy, and further, substantial anticariogenie efiicacy over and above stannous fluoride, SnF which in the same test provides ESR results ranging from to TABLE 1 In Vitro ESR on Whole Human Enamel Using Four Methods of Preparing the Fluoroxalate Complex at 9. Concentration Such as to Provide 1 The pH was adjusted to 5.0 with diluted OH.

Rat tooth ESR may be determined in vivo as follows. The teeth of a group of suitably selected test rats are given three thirty-second topical applications at thirty-minute intervals with solutions containing various alkali metal stannous fluoroxalate complexes. The animals are sacrificed one hour after the last treatment. Each mandibular hemijaw is removed, the clinical crowns of each are decalcified in 0.2 N pH sodium acetate buffer for twenty minutes, and the decalcification solutions are analyzed for phosphorus by a colorimetric method (Fisk and Subbarow, The Colorimetric Determination of Phosphorus, Journal of Biological Chemistry, 66:375, 1925). Phosphorus liberation of the teeth topically treated with the various alkali metal stannous fluoroxalate containing solutions was compared to that of teeth similarly treated with distilled water control solutions, and the result of such comparison is reported as a percentage reduction of enamel solubility (i.e., rat ESR). Table 2 presents the results of tests conducted using solutions of sodium and potassium difluoroxalatostannate(II) having a fluoride content of 1000 p.p.m. The data show an ESR value of over 74% for the fluoroxalatostannate complexes, as compared to control animals to which distilled Water was applied. By way of comparison, the ESR eifectiveness of a stannous fluoride solution containing 1000 p.p.m. F in the same test was 44.3%.

TABLE 2 The Effect of Different Fluoride Compounds in Aqueous Solution Upon the Rate of Acid Dissolution of Rat Enamel Procedure:

1. 5 rats were used per group 2. The animals were given three, thirty-second topical applications with the freshly prepared solutions. The pH was adjusted as needed with .1 N NaOH 3. One hour after the final topical the animals were sacrificed, the

hemijaws removed and the rate of dissolution of enamel determined as a function of the amount of phosphorus removed from the hemijaws by minute immersion in a .1N, pH 4.0 acetate buffer 1 Standard error of the mean.

Similar tests were performed using a dentifrice in vivo as follows. The teeth of a group of suitably selected test rats are given three thirty second applications at thirty minute intervals of a dentifrice with an active anticariogenie system composed of potassium difluoroxalatostannate(II) complexes, (F-lOOO p.p.m.), 0.15% fumaric acid and 2.5% victamide. The dentifrice has a pH of approximately 4.6. The animals are sacrificed one hour after the last brushing, and the ESR determined in accordance with the above procedure. The results of this test are presented in Table 3. These data illustrate an ESR value of 70% or better as compared to control animals. These data also illustrate that a commercially available fluoride containing dentifrice resulted in an ESR of 29% as compared to the control animals. Therefore, these data illustrate that a stannous difluoroxalatostannate(II) complex containing dentifrice has substantial anticariogenic eflicacy and substantial anticariogenic eflicacy over commeercially available fluoride containing dentifrices.

TABLE 3 The Effect of Different Dontifriee Formulations Upon the Rate of Enamel Dissolution in the Rat Procedure:

1. 5 animals were used per group.

2. The animals Were given three thirty-second brushings 3. One hour after the final brushing the animals were sacrificed, the hemijaws removed and the rate of dissolution of enamel deter mined as a function of the amount of phosphorus removed from the hemijaws by a 20-minute immersion period in a .1 N, pH 1.0 acetate buffer solution 1 Standard error of the mean.

ANIMAL TOXICITY In addition to exhibiting a high level of anticariogenic effectiveness, the difluoroxalatostannate(II) complexes of the present invention may be safely utilized in animal organisms without any dangerous side effects. The toX- icity of difiuoroxalatostannate(II) salts compare quite favorably with the other anticariogenic fluorides as shown by the following experimental studies. The acute toxicity of the difluoroxalatostannatc(II) complexes has been determined in mice (standard experimental animals for this purpose), and these data are given in Table 4. The toxicity is expressed in terms of an LD which is the lethal dose for 50% of the animals treated (within 24 hours).

TABLE 4 Comparative Acute Toxicity Data in Mice LDsn dosage Route of MgJF/kg. Mg. epd./kg

Fluoride compound administration body weight body Weight SnFg 35-36 -160 K2[SnF2(C2O 52 443 Na2[SnF2(C2O.1)] d0 61 468 Based on the data of Table 4 it would appear that the acute LD of potassium difluoroxalatostannate(II) is about 52 mg. F/ kg. body weight and the LD of sodium difluoroxalatostannate(II) is about 61 mg. F/kg. body weight. In comparison, the acute LD value for sodium fluoride is 36 mg. F/kg. body weight.

Thus, the difluoroxalatostannate(II) salts of this invention represent a substantial advance in the dental arts and provide safe and eifective adjuvants for use in oral compositions for dental caries prophylaxis.

What is claimed is:

1. Difiuoroxalatostannates of the formula where M is a member selected from the group consisting of potassium, sodium and ammonium.

2. A difiuoroxalatostannate, as claimed in claim 1, where M is sodium.

3. A difluoroxalatostannate, as claimed in claim 1, where M is potassium.

4. A difluoroxalatostannate, as claimed in claim 1, where M is ammonium.

References Cited UNITED STATES PATENTS 2,996,490 8/1961 Rowland et al. 260429.7

3,413,326 11/1968 Schmid 260429.7

3,448,132 6/1969 Griebstein 260429.7

WERTEN F. W. BELLAMY, Primary Examiner U.S. Cl. X.R. 

